For the past 18 years this grant has been instrumental in supporting and developing the activities of the Rheumatic Diseases Study Group. The main activities for which support is requested are the following: Immunology - 1. Amino acid sequence studies of the products of naturally occurring mutation of immunoglobulin producing cells in man in the hope of gaining insight into the organization of the Ig genes and to provide information regarding disorders of immunoglobulin synthesis in a variety of neoplastic and non-neoplastic diseases. 2. Studies on the organization of membrane proteins from normal, stimulated and transformed lymphoid cells. Amino acid sequence studies of IgD, the major immunoglobulin of lymphoid membranes are also contemplated. 3. Studies of the factors regulating immunoglobulin synthesis and assembly in a variety of disease states and under normal conditions. 4. Studies of the nature of factors liberated by plasma cell tumors which inhibit the immune response. Biochemistry - 1. An examination of the nature of the protein polysaccharides of bovine cartilage and especially the heterogeneity of the associated proteins with the hope of relating these findings to arthritis. 2. Studies of the specificity and biological function of two proteolytic enzymes isolated from mouse salivary glands with specificity for bonds involving arginine. Their use in protein sequencing studies and their possible role in gene expression will be examined. Cell Biology and Electron Microscopy - The role of thymic hormones in the differentiation of lymphoid and other blood forming cells in health and diseases. Clinical Pharmacology - The development of techniques to study the antiinflammatory effect of certain pharmacologic agents by measuring their analgesic properties and the possible interaction of chloroquin with DNA in relation to its therapeutic efficacy in SLE. It is our hope that ultimately these studies will bear directly on problems related to the pathogenesis of some of the connective tissue diseases.